Chitosan, which is derived from chitin, has drawn much attention due to its low toxicity and potential use in medical and pharmaceutical applications. The biological activities of chitosan have been shown to depend on its molecular weight (MW) and degree of deacetylation. In this study, we investigated whether oral chitooligosaccharides, which are easily absorbed into the body, can reduce the plasma level of lipid in smokers and non-smokers because smoking is a high-risk factor for cardiovascular diseases. All healthy men (11 smokers and 8 non-smokers) consumed 500 mg of chitooligosaccharides in water twice daily before a meal (breakfast and dinner) over a 6-week period. Total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased in both the smoker group and non-smoker group when compared with baseline. These results suggest that low MW chitooligosaccharides would be an effective dietary supplement for lowering cholesterol level.